Efficacy and Safety of Tabalumab, an Anti–B-Cell–Activating Factor Monoclonal Antibody, in a Heterogeneous Rheumatoid Arthritis Population. Issue 5 (August 2015)

• Record Type: Journal Article
• Authors: Genovese, Mark C.; Silverman, Gregg J.; Emery, Paul; Gupta, Ramesh C.; Gill, Anne; Veenhuizen, Melissa; Xie, Li; Komocsar, Wendy J.; Berclaz, Pierre-Yves; Lee, Chin
• Is Part Of: Journal of clinical rheumatology. Volume 21:Issue 5(2015:Aug.)
• Publication Date: 2015-08
• Subjects: Rheumatism -- Periodicals; Rheumatology -- Periodicals; Musculoskeletal system -- Diseases -- Periodicals; Musculoskeletal Diseases -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Rhumatologie -- Périodiques; Appareil locomoteur -- Maladies -- Périodiques; Musculoskeletal system -- Diseases; Rheumatism; Rheumatology; Periodicals; 616.723005
• DOI: 10.1097/RHU.0000000000000276
• Languages: English
• ISSNs: 1076-1608

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objectives</title> <p>The efficacy and safety of 2 different dosing regimens of tabalumab, a monoclonal antibody that neutralizes membrane-bound and soluble B-cell–activating factor (BAFF), were evaluated in patients with rheumatoid arthritis.</p> </sec> <sec> <title>Methods</title> <p>In this phase 3, multicenter, randomized study, 1004 patients (intention-to-treat population) received subcutaneous 120 mg tabalumab every 4 weeks (120/Q4W), 90 mg tabalumab every 2 weeks (90/Q2W), or placebo over 24 weeks. At baseline, a loading dose double the planned dose (ie, 240 mg, 180 mg, or placebo) was administered. Efficacy analyses were based on a prespecified subset of patients with 5 or more of 68 tender and 5 or more of 66 swollen joints at baseline (efficacy population, n = 849). The primary efficacy end point was ACR20 (20% improvement in American College of Rheumatology criteria) response at week 24.</p> </sec> <sec> <title>Results</title> <p>At week 24, there were no differences in ACR20 response rates (120/Q4W = 34.4%, 90/Q2W = 33.5%, placebo = 31.5%) or any other measures of efficacy across the treatment groups. Discontinuations due to adverse events (AE) were 3.4%, 2.7%, and 4.0%; incidence of treatment-emergent AEs were 64.1%, 58.2%, and 58.8%, with 23.2%, 25.9%, and 22.0% treatment-emergent infections; and incidence rates of serious AEs were 3.7%, 2.2%, and 2.8% with 1.1%, 0.3%, and 0.7% serious infections in the 120/Q4W, 90/Q2W, and placebo groups, respectively. Three deaths were reported (120/Q4W, n = 2; 90/Q2W, n = 1). Each tabalumab group had significant decreases versus placebo in CD3-CD20<sup>+</sup> B cells (<italic>P</italic> ⩽ 0.05) and in serum immunoglobulins (<italic>P</italic> ⩽ 0.001).</p> </sec> <sec> <title>Conclusions</title> <p>Although tabalumab administration resulted in biologic activity, as demonstrated by changes in B cells and immunoglobulins, targeting BAFF-dependent pathways alone is not sufficient to significantly reduce rheumatoid arthritis disease activity.</p> </sec> </abstract>